The specific aims of this proposal are to further delineate the neuronal mechanisms controlling rhythmical jaw movements (RJMs) resembling mastication in the guinea pig. We will combine electrophysiological, neuroanatomical, and neuropharmacological techniques to define the brainstem circuits and their underlying mechanisms responsible for rhythmical jaw movements induced by stimulation of the masticatory cortex. We propose to 1) determine the role of specific neuromessengers in controlling trigeminal premotoneuronal excitability during short pulse train cortical stimulation or during RJMs induced by repetitive cortical stimulation. 2) establish the location(s) of identified trigeminal premotoneurons which contain glutamate, serotonin, or norepinephrine, and 3) determine which subpopulation of trigeminal premotoneurons are specific targets of corticofugal afferents arising in masticatory cortex. The project is divided into two main parts. In part I, single cell recording and microiontophoretic ejection techniques will be utilized to determine the importance of specific neuromessengers in the control trigeminal premotoneuronal excitability during cortically induced RJMs. Identified premotoneurons will be recorded during cortically induced RJMs while simultaneously applying putative neuromessenger agonists and antagonists. Part II will focus on utilizing neuroanatomical and immunohistochemical techniques to further characterize the roles of trigeminal premotoneurons in RJM production. In the first set of experiments, we will combine immunohistochemical techniques for neurotransmitter identification with retrograde tracer techniques for trigeminal premontoneuronal localization of subpopulations of premotoneurons which contain the following neuromessengers: glutamate, serotonin, and norepinephrine. In the second series of experiments double labelling experiments will be performed to determine the subpopulation of trigeminal premotoneurons which specifically receive corticofugal input from masticatory cortex. The long-term goal of this research is to understand both the mechanism underlying the central nervous system control of normal rhythmic jaw movements that occur during activities such as feeding and drinking, as well as the abnormal. Involuntary, jaw movements occurring in disorders such as tardive dyskinesia, bruxism and myofascial pain dysfunction syndrome. The etiology of the generation of these abnormal jaw movements is unknown, although bruxism is thought to be related to stress, and tardive dyskinesia to a disruption of dopamine activity in the basal ganglia. The results of the proposed experiments in the guinea pig will provide insights into the neurophysiological and pharmacological mechanisms, as well as anatomical substrates at the brainstem level, underlying the production of involuntary rhythmic jaw movements in humans.